Chewable pharmaceutical dosage units, such as chewable tablets and soft-chewable tablets, are known and have been commercialized for pediatric, geriatric and involuntary (where subject by instinct will not accept the medication meant to be swallowed e.g. animals) patient populations. Chewable tablets are also of value to competent patients as an alternative to tablets or capsules that must be swallowed whole. The formulation of a drug into a chewable dosage form can increase patient acceptance of a medication in patients that resist or are unable to swallow conventional tablets or capsules.
The texture of a chewable dosage unit form is an important factor in the acceptance of oral dosage forms by patients in need of medication. Conventional dosage forms, such as chewable compressed tablets, using conventional ingredients, can make the tablet gritty or otherwise unappealing to many patients. Soft-chewable tablet dosage units, having a soft texture, pleasant mouth feel, and palatable taste with adequate flavoring agents, provide a solution to such problems. In addition, these features can address the problem of the disagreeable taste of many active pharmaceutical ingredients. Appropriate chewable dosage forms can also address texture problems caused by dry dusty, granular, and pulverant properties of many pharmaceutical ingredients.
A soft-chewable pharmaceutical dosage unit is a solid pharmaceutical dosage unit at room temperature that has low hardness and higher moisture content than a conventional tablet or hard chewable tablet. The dosage unit may be designed to be chewed and swallowed by a human or an animal. Such a dosage unit exhibits a plastic rheological behavior and can be formed by many manufacturing processes described in prior art into many different shapes. A soft-chewable pharmaceutical dosage unit after forming should be dimensionally stable. The ingredients of such a soft-chewable pharmaceutical dosage unit may be of pharmaceutical grade.
A semi plastic oral dosage form unit has a soft texture and hardness such that the unit is intended to be chewed and swallowed. The texture of the unit is such that it does not appreciably dissolve in the mouth. A semi plastic oral dosage form unit is formed by compression on rotary tablet press and exhibits hardness of less than 2 kilopond, preferably less than 1 kilopond, and more preferably has no measurable hardness when measured with a tablet hardness tester, which has excellent flexibility, is breakage and chip resistant and yet may be easily chewed and swallowed by human or animal.
Several soft-chewable pharmaceutical dosage units are described in the prior art. For example, U.S. Pat. No. 4,327,076 describes a soft-chew antacid tablet formed by blending three—premixes and compression, but without a granulation and sifting step. The tablets have a hardness of 3 kp (col. 9, top).
For example, U.S. Pat. No. 6,387,381 discloses an extrudate formed of a matrix having starch, sugar, fat, polyhydric alcohol and water.
A process for manufacturing soft-chewable dosage form for drug delivery is described in prior art U.S. Pat. No. 6,387,381. It discloses a soft-chewable medication vehicle for drug delivery of an active ingredient to animal or human subjects, not containing ingredients of animal origin, without use of heat and without addition of water. The formed mixture was formed into individual chunks using a Formax F6™ molding machine with dies for production of chunk-like shapes, and packaged for storage.
US 2014/0141055 discloses a process using a rotary molding machine for the manufacture of semi-plastic pharmaceutical unit doses that have lower hardness and higher moisture than conventional hard chewable tablets. The disclosed rotary molding process works by displacing dough between a rotary mold roller and removal from the mold without a punch mechanism.
WO 2004/014143 discloses compositions and processes for the delivery of an additive to an organism in a form suitable for consumption, including in the form of a soft-chew composition.
US 2009/0280159 and US 2011/0223234 relate to palatable edible soft-chewable medication vehicles. The processes described in these publications relate to the problem that heat generated during the extrusion process causes deterioration in the stability of the active ingredient in the mixture.
Machines for the production of molded food patties have been described to be useful for the manufacturing of soft-chews for administration to non-human animals. Such machines are molding machines that have been originally developed for use in producing molded food products, for example the Formax F6™ molding machine made by the Formax Corporation or the molding machines disclosed in U.S. Pat. Nos. 3,486,186; 3,887,964; 3,952,478; 4,054,967; 4,097,961; 4,182,003; 4,334,339; 4,338,702; 4,343,068; 4,356,595; 4,372,008; 4,535,505; 4,597,135; 4,608,731; 4,622,717; 4,697,308; 4,768,941; 4,780,931; 4,818,446; 4,821,376; 4,872,241; 4,975,039; 4,996,743; 5,021,025; 5,022,888; 5,655,436; and 5,980,228.
The use of extruders, forming machines and rotary molding machines exhibit problems associated with the weight and physical forms of a final dosage form. Moreover, the use of such technologies may require conditioning of the final dosage form (e.g. drying or curing final formed structure) for consolidation of shape and structure of formed structure.
The use of such technologies, equipment and processes is complex, cumbersome, and something that is not traditionally used in a typical pharmaceutical oral solid dosage form manufacturing facility.
A tablet press is a mechanical device that compresses powder into tablets of uniform size and weight. A press can be used to manufacture tablets/pellets of a wide variety of materials, including pharmaceuticals, cleaning products, and cosmetics. There are two types of press machines, eccentric-type and rotary-type. The rotary-type is generally more widely used, because it facilitates high production performance with narrow weight variation along with ease of use.
Accordingly, alternate processes for manufacturing soft-chew tablet formulations on a large scale using commonly installed pharmaceutical manufacturing equipment using such as a rotary (tablet) compression press would is desirable.